What does STAT4 do?
The STAT4 gene provides instructions for a protein that acts as a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of certain genes.
What activates STAT4?
STAT4 is predominantly activated in response to IL-12, which drives T-helper cell differentiation towards the Th1 and Th17 pathways. The phenotype of STAT4-deficient mice is very similar to that of mice lacking IL-12.
Is STAT5 a transcription factor?
Development of T Cell Immunity STAT5 serves as a signaling unit and transcription factor for cytokine receptors that utilize the common gamma chain (γc). These γc-dependent cytokines include IL-2, IL-7, and IL-15.
What secretes il12?
IL-12 is predominantly produced by dendritic cells, monocytes, and macrophages, and to a lesser extent by B-cells. IL-12 is widely accepted as an important regulator of Th1 responses. It also promotes the expansion and survival of activated T-cells and NK cells and modulates the cytotoxic activity of CTLs and NK cells.
What is the STAT5 pathway?
STAT3 and STAT5 proteins are oncogenic downstream mediators of the JAK–STAT pathway. Deregulated STAT3 and STAT5 signaling promotes cancer cell proliferation and survival in conjunction with other core cancer pathways.
What genes does STAT5 regulate?
Activation of the Immune System STAT5 regulates the transcription of the Il4 gene by binding two DNase I hypersensitivity sites, HSII and HSIII, and regulating accessibility to the gene (Zhu et al., 2003; Cote-Sierra et al., 2004).
What induces IL-12?
The production of IL-12 is induced by microbial signals such as lipopolysaccharide (LPS) or CpG bacterial DNA motifs (9,10), by activated T cell signals mediated by CD40–CD40 ligand (CD40L) (11), and further regulated by cytokines such as IFN-γ, IL-4 and granulocyte macrophage colony stimulating factor (GM-CSF) (12,13) …
What activates IL-12?
IL-12 is able to activate all major cytotoxic killer and helper cell types of the immune apparatus (NK, NKT, CD4 +, and CD8 + T cells) that are crucially important for immunosurveillance of and resistance to cancer development and progression 93.
What is STAT5 in biology?
Signal transducer and activator of transcription 5 (STAT5) refers to two highly related proteins, STAT5A and STAT5B, which are part of the seven-membered STAT family of proteins. STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes.
What is phospho STAT5?
Phosphorylated STAT5 forms homo- and heterodimers that translocate to the nucleus, leading to the transcription of target genes including the IL-2Rα gene.
What is the main function of IL-12?
Key Points Interleukin-12 (IL-12) is a heterodimeric pro-inflammatory cytokine that regulates T-cell and natural killer-cell responses, induces the production of interferon-γ (IFN-γ), favours the differentiation of T helper 1 (TH1) cells and is an important link between innate resistance and adaptive immunity.
Is IL-12 anti inflammatory?
IL-12 can aid in the activation and regulation of several cytotoxic immune cells including macrophages, natural killer cells, and T cells, thus making it a ‘pro-inflammatory cytokine’.
What is function of STAT4 in autoimmune cells?
STAT4 encodes the signal transducer and activator of transcription 4 protein (STAT4), which transmits signals from the receptor for type I IFN, IL-12 and IL-23, and can contribute to autoimmune responses by affecting the functions of several innate and adaptive immune cells (122).
How is STAT4 an activator of gene expression?
Signal transducer and activator of transcription 4 (STAT4) is a member of the STAT family and localizes to the cytoplasm. STAT4 is phosphorylated after a variety of cytokines bind to the membrane, and then dimerized STAT4 translocates to the nucleus to regulate gene expression.
How is IL-12 related to STAT4 signaling?
IL-12 drives small airway remodeling via STAT4 signaling. These data demonstrate that STAT4 regulates the respiratory syncytial virus-specific CD8+ T cell response to secondary infection but does not independently regulate lung Th2 or Th17 immune responses.
Why is STAT4 important in the JAK-STAT pathway?
In JAK-STAT pathway, STAT4 was first discovered to be crucial for promoting cellular-mediated immune responses via the differentiation of Th1 cells [ 3 ]. STAT4 protein contains six domains that have different functions in the JAK-STAT pathway: 1.